Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery
Open accessAbstract
Nanoparticle-mediated siRNA delivery is a complex process that requires transport across numerous extracellular and intracellular barriers. As such, the development of nanoparticles for efficient delivery would benefit from an understanding of how parameters associated with these barriers relate to the physicochemical properties of nanoparticles. Here, we use a multiparametric approach for the evaluation of lipid nanoparticles (LNPs) to identify relationships between structure, biological function, and biological activity. Our results indicate that evaluation of multiple parameters associated with barriers to delivery such as siRNA entrapment, pK a , LNP stability, and cell uptake as a collective may serve as a useful prescreening tool for the advancement of LNPs in vivo. This multiparametric approach complements the use of in vitro efficacy results alone for prescreening and improves in vitro–in vivo translation by minimizing false negatives. For the LNPs used in this work, the evaluation of multiple parameters enabled the identification of LNP pK a as one of the key determinants of LNP function and activity both in vitro and in vivo. It is anticipated that this type of analysis can aid in the identification of meaningful structure–function–activity relationships, improve the in vitro screening process of nanoparticles before in vivo use, and facilitate the future design of potent nanocarriers.
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Endosomal escape can be increased by optimizing the pKa values of ionizable lipids.
“Endosomal escape can be increased by optimizing the pKa values of ionizable lipids66,76–78,88,100,140.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [140]
The delivery efficacy of mRNA could be improved by rational design of lipids through modulation of head groups and hydrophobic tails to increase cellular uptake and endosomal escape of lipid nanoparticle-mRNA formulations.
“Moreover, the delivery efficacy of mRNA could be improved, for example, by rational design of lipids through modulation of head groups and hydrophobic tails to increase cellular uptake and endosomal escape of lipid nanoparticle–mRNA formulations64,66,76–78,88,97,100,114,140,141.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [140]
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Knocking down barriers: advances in siRNA delivery
Whitehead, K. A., Langer, R., & Anderson, D. G. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2742 · Cited by 3,115 · see citing works
Self-citationThe effect of particle design on cellular internalization pathways
Gratton, S. E. A., Ropp, P. A., Pohlhaus, P. D., Luft, J. C., Madden, V. J., Napier, M. E., & DeSimone, J. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801763105 · Cited by 2,918 · see citing works
Rational design of cationic lipids for siRNA delivery
Semple, S. C., Akinc, A., Chen, J., Sandhu, A. P., Mui, B. L., Cho, C. K., Sah, D. W. Y., Stebbing, D., Crosley, E. J., Yaworski, E., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1602 · Cited by 1,822 · see citing works
Endosomal escape pathways for delivery of biologicals
Varkouhi, A. K., Scholte, M., Storm, G., & Haisma, H. J. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.004 · Cited by 1,561 · see citing works
Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo
Jayaraman, M., Ansell, S. M., Mui, B. L., Tam, Y. K., Chen, J., Du, X., Butler, D., Eltepu, L., Matsuda, S., Narayanannair, J. K., et al. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201203263 · Cited by 1,267 · see citing works
Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms
Akinc, A., Querbes, W., De, S., Qin, J., Frank-Kamenetsky, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Cantley, W. L., Dorkin, J. R., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.85 · Cited by 1,261 · see citing works
A combinatorial library of lipid-like materials for delivery of RNAi therapeutics
Akinc, A., Zumbuehl, A., Goldberg, M. S., Leshchiner, E. S., Busini, V., Hossain, N., Bacallado, S., Nguyen, D. N., Fuller, J. E., Alvarez, R., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1402 · Cited by 1,228 · see citing works
Self-citationDavis, M. E. (2009) · Molecular Pharmaceutics · doi:10.1021/mp900015y · Cited by 979 · see citing works
Lipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969 · see citing works
Self-citationTherapeutic siRNA silencing in inflammatory monocytes in mice
Leuschner, F., Dutta, P., Gorbatov, R., Novobrantseva, T. I., Donahoe, J. S., Courties, G., Lee, K. M., Kim, J. I., Markmann, J. F., Marinelli, B., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1989 · Cited by 839 · see citing works
Self-citationDelivery of siRNA Therapeutics: Barriers and Carriers
Wang, J., Lu, Z., Wientjes, M. G., & Au, J. L. ‐. (2010) · The AAPS Journal · doi:10.1208/s12248-010-9210-4 · Cited by 804 · see citing works
Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes
Rozema, D. B., Lewis, D. L., Wakefield, D. H., Wong, S. C., Klein, J. J., Roesch, P. L., Bertin, S. L., Reppen, T. W., Chu, Q., Blokhin, A. V., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703778104 · Cited by 658 · see citing works
Breaking down the barriers: siRNA delivery and endosome escape
Domińska, M., & Dykxhoorn, D. M. (2010) · Journal of Cell Science · doi:10.1242/jcs.066399 · Cited by 632 · see citing works
Bartlett, D. W. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj439 · Cited by 593 · see citing works
Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids
Heyes, J., Palmer, L., Bremner, K., & MacLachlan, I. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.06.014 · Cited by 572 · see citing works
A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium
Santel, A., Aleku, M., Keil, O., Endruschat, J., Esche, V., Fisch, G., Dames, S., Löffler, K., Fechtner, M., Arnold, W., et al. (2006) · Gene Therapy · doi:10.1038/sj.gt.3302777 · Cited by 368 · see citing works
Development of Lipidoid–siRNA Formulations for Systemic Delivery to the Liver
Akinc, A., Goldberg, M. S., Qin, J., Dorkin, J. R., Gamba‐Vitalo, C., Maier, M. A., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Manoharan, M., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.36 · Cited by 353 · see citing works
Self-citationNucleic Acid Delivery: The Missing Pieces of the Puzzle?
Nguyen, J., & Szoka, F. C. (2012) · Accounts of Chemical Research · doi:10.1021/ar3000162 · Cited by 347 · see citing works
pH Homeostasis of Cellular Organelles
Demaurex, N. (2002) · Physiology · doi:10.1152/physiologyonline.2002.17.1.1 · Cited by 234 · see citing works
Extracellular Glycosaminoglycans Modify Cellular Trafficking of Lipoplexes and Polyplexes
Ruponen, M., Rönkkö, S., Honkakoski, P., Pelkonen, J., Tammi, M., & Urtti, A. O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011553200 · Cited by 208 · see citing works
Merkel, O. M., Librizzi, D., Pfestroff, A., Schurrat, T., Buyens, K., Sanders, N. N., Smedt, S. C. D., Béhé, M. P., & Kissel, T. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.05.016 · Cited by 183 · see citing works
Modulation of Membrane Fusion by Asymmetric Transbilayer Distributions of Amino Lipids
Bailey, A. L., & Cullis, P. R. (1994) · Biochemistry · doi:10.1021/bi00208a007 · Cited by 143 · see citing works
Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells
Novobrantseva, T. I., Borodovsky, A., Wong, J., Klebanov, B., Zafari, M. R., Yucius, K., Querbes, W., Ge, P., Ruda, V. M., Milstein, S., et al. (2012) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2011.3 · Cited by 135 · see citing works
Self-citationBuyens, K., Lucas, B., Raemdonck, K., Braeckmans, K., Vercammen, J., Hendrix, J., Engelborghs, Y., Smedt, S. C. D., & Sanders, N. N. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.10.024 · Cited by 133 · see citing works
In Vitro–In Vivo Translation of Lipid Nanoparticles for Hepatocellular siRNA Delivery
Whitehead, K. A., Matthews, J., Chang, P., Niroui, F., Dorkin, J. R., Severgnini, M., & Anderson, D. G. (2012) · ACS Nano · doi:10.1021/nn301922x · Cited by 130 · see citing works
Self-citationHobo, W. A., Novobrantseva, T. I., Fredrix, H., Wong, J., Milstein, S., Epstein-Barash, H., Liu, J., Schaap, N. P., van der Voort, R., & Dolstra, H. (2012) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-012-1334-1 · Cited by 127 · see citing works
Kwon, Y. J. (2011) · Accounts of Chemical Research · doi:10.1021/ar200241v · Cited by 127 · see citing works
Quantitative Analysis of Synthetic Gene Delivery Vector Design Properties
Varga, C. M., Hong, K., & Lauffenburger, D. A. (2001) · Molecular Therapy · doi:10.1006/mthe.2001.0475 · Cited by 120 · see citing works
Cell‐surface glycosaminoglycans inhibit cation‐mediated gene transfer
Ruponen, M., Honkakoski, P., Tammi, M., & Urtti, A. O. (2004) · The Journal of Gene Medicine · doi:10.1002/jgm.522 · Cited by 112 · see citing works
Tang, Y., Li, Y.-B., Wang, B., Lin, R.-Y., van Dongen, M. A., Zurcher, D. M., Gu, X.-Y., Holl, M. M. B., Liu, G., & Qi, R. (2012) · Molecular Pharmaceutics · doi:10.1021/mp3001364 · Cited by 99 · see citing works
Zhang, J., Fan, H., Levorse, D. A., & Crocker, L. S. (2011) · Langmuir · doi:10.1021/la104590k · Cited by 95 · see citing works
Philipp, A. B., Zhao, X. B., Tarcha, P. J., Wagner, E., & Zintchenko, A. (2009) · Bioconjugate Chemistry · doi:10.1021/bc9001536 · Cited by 87 · see citing works
Phospholipid, cholesterol, polypeptide and glycoprotein composition of hepatic endosome subfractions
Evans, W. H., & Hardison, W. G. M. (1985) · Biochemical Journal · doi:10.1042/bj2320033 · Cited by 83 · see citing works
FRET-Labeled siRNA Probes for Tracking Assembly and Disassembly of siRNA Nanocomplexes
Alabi, C. A., Love, K. T., Sahay, G., Stutzman, T., Young, W. T., Langer, R., & Anderson, D. G. (2012) · ACS Nano · doi:10.1021/nn3013838 · Cited by 67 · see citing works
Self-citationAttacking the genome: emerging siRNA nanocarriers from concept to clinic
Alabi, C. A., Vegas, A. J., & Anderson, D. G. (2012) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2012.05.004 · Cited by 53 · see citing works
Self-citationZhang, J., Fan, H., Levorse, D. A., & Crocker, L. S. (2011) · Langmuir · doi:10.1021/la201464k · Cited by 48 · see citing works
Sulakhe, P. V., & Dhalla, N. S. (1970) · PubMed · Cited by 46 · see citing works
Mescalchin, A., Detzer, A., Wecke, M., Overhoff, M. G., Wünsche, W., & Sczakiel, G. (2007) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.7.10.1531 · Cited by 40 · see citing works
Nanocarriers: a tool to overcome biological barriers in siRNA delivery
Kumari, A., Kumar, V., & Yadav, S. K. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.587801 · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [29]Fitzgerald K et al. (2012) Phase I safety, pharmacokinetic and pharmacodynamic results for ALN-PCS: A novel RNAi therapeutic for the treatment of hypercholesterolemia (Alnylam Pharmaceuticals, Cambridge, MA). Available at http://www.alnylam. com/capella/wp-content/uploads/2012/04/ALN-PCS-PhaseI-ATVB-April20-2012.pdf. Accessed September 8, 2012.
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Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076 · see citing works
Self-citationNon-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123 · see citing works
Self-citationmRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555 · see citing works
Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown
Wittrup, A., Ai, A., Liu, X., Hamar, P., Trifonova, R., Charisse, K., Manoharan, M., Kirchhausen, T., & Lieberman, J. (2015) · Nature Biotechnology · doi:10.1038/nbt.3298 · Cited by 693 · see citing works
Liu, S., Cheng, Q., Wei, T., Yu, X., Johnson, L. T., Farbiak, L., & Siegwart, D. J. (2021) · Nature Materials · doi:10.1038/s41563-020-00886-0 · Cited by 653 · see citing works
Lipids and Lipid Derivatives for RNA Delivery
Zhang, Y., Sun, C., Wang, C., Jankovic, K. E., & Dong, Y. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00244 · Cited by 638 · see citing works
Strategies, design, and chemistry in siRNA delivery systems
Dong, Y., Siegwart, D. J., & Anderson, D. G. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.05.004 · Cited by 581 · see citing works
Self-citationIntegrating Artificial Intelligence and Nanotechnology for Precision Cancer Medicine
Adir, O., Poley, M., Chen, G., Froim, S., Krinsky, N., Shklover, J., Shainsky‐Roitman, J., Lammers, T., & Schroeder, A. (2020) · Advanced Materials · doi:10.1002/adma.201901989 · Cited by 496 · see citing works
Surface-Engineered Dendrimers in Gene Delivery
Jiepin, Y., Zhang, Q., Chang, H., & Cheng, Y. (2015) · Chemical Reviews · doi:10.1021/cr500542t · Cited by 432 · see citing works
Kim, M., Jeong, M., Hur, S., Cho, Y., Park, J., Jung, H. R., Seo, Y., Woo, H., Nam, K. T., Lee, K., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf4398 · Cited by 390 · see citing works
Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver
Miao, L., Lin, J., Huang, Y., Li, L., Delcassian, D., Ge, Y., Shi, Y., & Anderson, D. G. (2020) · Nature Communications · doi:10.1038/s41467-020-16248-y · Cited by 343 · see citing works
Self-citationThe Importance of Apparent pKa in the Development of Nanoparticles Encapsulating siRNA and mRNA
Patel, P., Ibrahim, N. M., & Cheng, K. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.03.002 · Cited by 293 · see citing works
Zhai, J., Fong, C., Tran, N. L., & Drummond, C. J. (2019) · ACS Nano · doi:10.1021/acsnano.8b07961 · Cited by 281 · see citing works
Wang, M., Alberti, K. A., Sun, S., Arellano, C. L., & Xu, Q. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201311245 · Cited by 250 · see citing works
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Ma, D. (2014) · Nanoscale · doi:10.1039/c4nr00018h · Cited by 203 · see citing works
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Rietwyk, S., & Peer, D. (2017) · ACS Nano · doi:10.1021/acsnano.7b04734 · Cited by 199 · see citing works
Zhou, K., Nguyen, L. H., Miller, J. B., Yan, Y., Kós, P., Xiong, H., Li, L., Hao, J., Minnig, J. T., Zhu, H., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520756113 · Cited by 184 · see citing works
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Zhao, Y. D., & Huang, L. (2014) · Advances in genetics · doi:10.1016/b978-0-12-800148-6.00002-x · Cited by 182 · see citing works
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Li, B., Zhang, X., & Dong, Y. (2019) · WIREs Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1530 · Cited by 170 · see citing works
Green Tea Catechin Dramatically Promotes RNAi Mediated by Low-Molecular-Weight Polymers
Shen, W., Wang, Q., Shen, Y., Gao, X., Li, L., Yan, Y., Wang, H., & Cheng, Y. (2018) · ACS Central Science · doi:10.1021/acscentsci.8b00363 · Cited by 169 · see citing works
Leveraging Physiology for Precision Drug Delivery
Sun, W., Hu, Q., Ji, W., Wright, G., & Gu, Z. (2017) · Physiological Reviews · doi:10.1152/physrev.00015.2016 · Cited by 169 · see citing works
Recent Advances in Nanoparticle-Mediated siRNA Delivery
Williford, J., Wu, J., Ren, Y., Archang, M. M., Leong, K. W., & Mao, H. (2014) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071813-105119 · Cited by 156 · see citing works
Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature
Khan, O. F., Zaia, E. W., Jhunjhunwala, S., Xue, W., Cai, W., Yun, D. S., Barnés, C. M., Dahlman, J. E., Dong, Y., Pelet, J. M., et al. (2015) · Nano Letters · doi:10.1021/nl5048972 · Cited by 137 · see citing works
Self-citationChaudhary, N., Kasiewicz, L. N., Newby, A. N., Arral, M. L., Yerneni, S. S., Melamed, J. R., LoPresti, S. T., Fein, K. C., Petersen, D. M. S., Kumar, S., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01256-w · Cited by 137 · see citing works
Kumar, R., Le, N., Tan, Z., Brown, M. E., Jiang, S., & Reineke, T. M. (2020) · ACS Nano · doi:10.1021/acsnano.0c08549 · Cited by 127 · see citing works
Raftery, R. M., Walsh, D., Castaño, I. M., Heise, A., Duffy, G., Cryan, S., & O'Brien, F. (2016) · Advances in Materials · doi:10.1002/adma.201505088 · Cited by 104 · see citing works
How successful is nuclear targeting by nanocarriers?
Tammam, S. N., Azzazy, H. M. E.-S., & Lamprecht, A. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.03.022 · Cited by 108 · see citing works
Tang, C., Jing, W., Han, K. S., Yang, Z., Zhang, S., Liu, M., Zhang, J., Zhao, X., Liu, Y., Shi, C., et al. (2024) · ACS Nano · doi:10.1021/acsnano.3c10109 · Cited by 100 · see citing works
Lipid Nanoparticles for Delivery of Therapeutic RNA Oligonucleotides
Moss, K. H., Popova, P. G., Hadrup, S. R., Astakhova, K., & Taskova, M. (2019) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b01290 · Cited by 99 · see citing works
Xiong, H., Liu, S., Wei, T., Cheng, Q., & Siegwart, D. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.06.030 · Cited by 64 · see citing works
Direct Cytosolic Delivery of siRNA Using Nanoparticle‐Stabilized Nanocapsules
Jiang, Y. Y., Tang, R., Duncan, B., Jiang, Z., Yan, B., Mout, R., & Rotello, V. M. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201409161 · Cited by 90 · see citing works
Functional polyesters enable selective siRNA delivery to lung cancer over matched normal cells
Yan, Y., Liu, L., Xiong, H., Miller, J. B., Zhou, K., Kós, P., Huffman, K. E., Elkassih, S. A., Norman, J. W., Carstens, R. M., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1606886113 · Cited by 88 · see citing works
siRNA Functionalized Lipid Nanoparticles (LNPs) in Management of Diseases
Kalita, T., Dezfouli, S. A., Pandey, L. M., & Uludağ, H. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14112520 · Cited by 87 · see citing works
Li, Y., Yang, T., Yu, Y., Shi, N., Yang, L., Glass, Z., Bolinger, J., Finkel, I. J., Li, W., & Xu, Q. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.03.011 · Cited by 84 · see citing works
TGFβ signaling pathways in human health and disease
Chen, P., Qin, L., & Simons, M. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1113061 · Cited by 84 · see citing works
Lipid Nanoparticle Delivery Systems to Enable mRNA-Based Therapeutics
Semple, S. C., Leone, R. D., Barbosa, C., Tam, Y. K., & Lin, P. J. C. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020398 · Cited by 80 · see citing works
Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles
Rodríguez‐Gascón, A., del Pozo‐Rodríguez, A., & Solinís, M. Á. (2014) · International Journal of Nanomedicine · doi:10.2147/ijn.s39810 · Cited by 79 · see citing works
Cui, L., Hunter, M. R., Sonzini, S., Pereira, S. G. T., Romanelli, S. M., Liu, K., Li, W., Liang, L., Yang, B., Mahmoudi, N., et al. (2021) · Small · doi:10.1002/smll.202105832 · Cited by 78 · see citing works
Zhou, J., Wu, Y., Wang, C., Cheng, Q., Han, S., Wang, X., Zhang, J., Deng, L., Zhao, D., Du, L., et al. (2016) · Nano Letters · doi:10.1021/acs.nanolett.6b02915 · Cited by 78 · see citing works
Synthetic multi-layer nanoparticles for CRISPR-Cas9 genome editing
Tang, H., Zhao, X., & Jiang, X. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.03.001 · Cited by 76 · see citing works
Targeted lipid nanoparticles for RNA therapeutics and immunomodulation in leukocytes
Veiga, N., Diesendruck, Y., & Peer, D. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.04.002 · Cited by 74 · see citing works
Non-viral nanoparticles for RNA interference: Principles of design and practical guidelines
Liu, Z., Wang, S., Tapeinos, C., Torrieri, G., Känkänen, V., El‐Sayed, N., Python, A., Hirvonen, J. J., & Santos, H. A. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.05.018 · Cited by 70 · see citing works
Yu, H., Angelova, A., Angelov, B., Dyett, B., Matthews, L., Zhang, Y., Mohamad, M. E., Cai, X., Valimehr, S., Drummond, C. J., et al. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202304977 · Cited by 70 · see citing works
Zhang, H., & Barz, M. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.02.055 · Cited by 77 · see citing works
Altınoglu, S., Wang, M., & Xu, Q. (2015) · Nanomedicine · doi:10.2217/nnm.14.192 · Cited by 68 · see citing works
Assembly strategy of liposome and polymer systems for siRNA delivery
Song, H., Hart, S. L., & Du, Z. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.120033 · Cited by 67 · see citing works
Combinatorial Approach to Nanoarchitectonics for Nonviral Delivery of Nucleic Acids
Molla, M. R., & Levkin, P. A. (2015) · Advanced Materials · doi:10.1002/adma.201502888 · Cited by 62 · see citing works
Werfel, T. A., Jackson, M. A., Kavanaugh, T. E., Kirkbride, K. C., Miteva, M., Giorgio, T. D., & Duvall, C. L. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.03.389 · Cited by 61 · see citing works
pH-Dependent Phase Behavior and Stability of Cationic Lipid–mRNA Nanoparticles
Larson, N. R., Hu, G., Wei, Y., Tuesca, A. D., Forrest, M. L., & Middaugh, C. R. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.11.004 · Cited by 60 · see citing works
Wang, M., Alberti, K. A., Sun, S., Arellano, C. L., & Xu, Q. (2014) · Angewandte Chemie · doi:10.1002/ange.201311245 · Cited by 59 · see citing works
Suzuki, Y., & Ishihara, H. (2016) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2016.06.124 · Cited by 57 · see citing works
Du, L., Wang, C., Meng, L., Cheng, Q., Zhou, J., Wang, X., Zhao, D., Zhang, J., Deng, L., Liang, Z., et al. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.05.046 · Cited by 56 · see citing works
Sita, T. L., Kouri, F. M., Hurley, L., Merkel, T. J., Chalastanis, A., May, J., Tommasini-Ghelfi, S., Cole, L. E., Cayton, T. C., Barnaby, S. N., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1702736114 · Cited by 55 · see citing works
Cationic switchable lipids: pH-triggered molecular switch for siRNA delivery
Viricel, W., Poirier, S., Mbarek, A., Derbali, R. M., Mayer, G., & Chain, J. L. (2016) · Nanoscale · doi:10.1039/c6nr06701h · Cited by 54 · see citing works
Yu, H., Iscaro, J., Dyett, B., Zhang, Y., Seibt, S., Martínez, N. P., White, J., Drummond, C. J., Bozinovski, S., & Zhai, J. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c08729 · Cited by 52 · see citing works
Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery
Haque, M. A., Shrestha, A., Mikelis, C. M., & Mattheolabakis, G. (2024) · International Journal of Pharmaceutics X · doi:10.1016/j.ijpx.2024.100283 · Cited by 49 · see citing works
Lipid-based nanocarriers for delivery of small interfering RNA for therapeutic use
Parashar, D., Rajendran, V., Shukla, R., & Sistla, R. (2019) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2019.105159 · Cited by 47 · see citing works
Therapeutic Applications of Spherical Nucleic Acids
Barnaby, S. N., Sita, T. L., Petrosko, S. H., Stegh, A. H., & Mirkin, C. A. (2015) · Cancer treatment and research · doi:10.1007/978-3-319-16555-4_2 · Cited by 46 · see citing works
Jung, O., Jung, H., Thủy, L. T. T., Choi, M., Kim, S., Jeon, H., Yang, J., Kim, S., Kim, T., Lee, E., et al. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202303857 · Cited by 45 · see citing works
Xu, Y., Gong, F., Golubovic, A., Strilchuk, A. W., Chen, J., Zhou, M., Dong, S., Seto, B. Y., & Li, B. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2409572122 · Cited by 47 · see citing works
Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA
Li, B., Luo, X. L., Deng, B., Giancola, J. B., McComb, D. W., Schmittgen, T. D., & Dong, Y. (2016) · Scientific Reports · doi:10.1038/srep22137 · Cited by 44 · see citing works
Scomparin, A., Polyak, D., Krivitsky, A., & Satchi‐Fainaro, R. (2015) · Biotechnology Advances · doi:10.1016/j.biotechadv.2015.04.008 · Cited by 43 · see citing works
Chan, C., Du, S., Dong, Y., & Cheng, X. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666201126162945 · Cited by 45 · see citing works
Nanoscale delivery platforms for RNA therapeutics: Challenges and the current state of the art
Rhym, L. H., & Anderson, D. G. (2022) · Med · doi:10.1016/j.medj.2022.02.001 · Cited by 45 · see citing works
Self-citationScreening of efficient siRNA carriers in a library of surface-engineered dendrimers
Liu, H., Chang, H. Y., Lv, J., Jiang, C., Li, Z., Wang, F., Wang, H., Wang, M., Liu, C., Wang, X., et al. (2016) · Scientific Reports · doi:10.1038/srep25069 · Cited by 42 · see citing works
High-throughput platforms for machine learning-guided lipid nanoparticle design
Hanna, A. R., Issadore, D., & Mitchell, M. J. (2025) · Nature Reviews Materials · doi:10.1038/s41578-025-00831-0 · Cited by 43 · see citing works
Miller, J. B., & Siegwart, D. J. (2018) · Nano Research · doi:10.1007/s12274-018-2099-4 · Cited by 40 · see citing works
Yu, H., Dyett, B., Drummond, C. J., & Zhai, J. (2025) · Accounts of Chemical Research · doi:10.1021/acs.accounts.5c00522 · Cited by 40 · see citing works
lncRNA in the liver: Prospects for fundamental research and therapy by RNA interference
Smekalova, E. M., Kotelevtsev, Y. V., Leboeuf, D., Shcherbinina, E. Y., Fefilova, A. S., Zatsepin, T. S., & Koteliansky, V. (2016) · Biochimie · doi:10.1016/j.biochi.2016.06.007 · Cited by 39 · see citing works
High-throughput screening of nanoparticles in drug delivery
Tomé, I., Francisco, V., Fernandes, H., & Ferreira, L. (2021) · APL Bioengineering · doi:10.1063/5.0057204 · Cited by 38 · see citing works
Silicon Ether Ionizable Lipids Enable Potent mRNA Lipid Nanoparticles with Rapid Tissue Clearance
Holland, R., Lam, K., Jeng, S. C. Y., McClintock, K., Palmer, L., Schreiner, P., Wood, M., Zhao, W., & Heyes, J. A. (2024) · ACS Nano · doi:10.1021/acsnano.3c09028 · Cited by 38 · see citing works
Ray, P., Nair, G., Ghosh, A., Banerjee, S., Golovko, M. Y., Banerjee, S. K., Reindl, K. M., Mallik, S., & Quadir, M. (2019) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-019-00514-w · Cited by 36 · see citing works
Kirtane, A. R., Bi, J., Rajesh, N. U., Tang, C., Jiménez, M., Witt, E., McGovern, M. K., Cafi, A. B., Hatfield, S. J., Rosenstock, L., et al. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01360-5 · Cited by 36 · see citing works
Ma, D., Tian, S., Baryza, J. L., Luft, J. C., & DeSimone, J. M. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00054 · Cited by 36 · see citing works
Determining the Surface pKa of Perfluorooctanoic Acid
Musegades, L. J., Curtin, O. P., & Cyran, J. D. (2024) · The Journal of Physical Chemistry C · doi:10.1021/acs.jpcc.3c07235 · Cited by 35 · see citing works
Development of amino acid-modified biodegradable lipid nanoparticles for siRNA delivery
Patel, P., Fetse, J., Lin, C., Guo, Y., Hasan, M. R., Nakhjiri, M., Zhao, Z., Jain, A., & Cheng, K. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.09.065 · Cited by 36 · see citing works
Rodríguez‐Gascón, A., del Pozo‐Rodríguez, A., Isla, A., & Solinís, M. Á. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.07.002 · Cited by 34 · see citing works
siRNA-nanoparticle conjugate in gene silencing: A future cure to deadly diseases?
Acharya, R., Saha, S., Ray, S., Hazra, S., Mitra, M. K., & Chakraborty, J. (2017) · Materials Science and Engineering C · doi:10.1016/j.msec.2017.03.009 · Cited by 33 · see citing works
The development of an in vitro assay to screen lipid based nanoparticles for siRNA delivery
Zhang, Y., Arrington, L., Boardman, D., Davis, J., Xu, Y., DiFelice, K., Stirdivant, S. M., Wang, W., Budzik, B., Bawiec, J., et al. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.11.006 · Cited by 32 · see citing works
Shen, Q., Liu, J., Zeng, L., Ren, Y., Liao, J., Chen, S., Tang, Y., Zhang, Z., Jiang, M., Liao, H., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113588 · Cited by 30 · see citing works
Concepts and Application of DNA Origami and DNA Self-Assembly: A Systematic Review
Liu, W., Duan, H., Zhang, D., Zhang, X., Luo, Q., Xie, T., Yan, H., Peng, L., Hu, Y., Li, L., et al. (2021) · Applied Bionics and Biomechanics · doi:10.1155/2021/9112407 · Cited by 30 · see citing works
Yu, H., Dyett, B., Kirby, N. M., Cai, X., Mohamad, M. E., Bozinovski, S., Drummond, C. J., & Zhai, J. (2024) · Small · doi:10.1002/smll.202309200 · Cited by 29 · see citing works
Design principles of lipid nanoparticles for RNA delivery
Arral, M. L., & Whitehead, K. A. (2026) · Nature Reviews Bioengineering · doi:10.1038/s44222-026-00401-1 · Cited by 36 · see citing works
Catalytic self-assembly of a DNA dendritic complex for efficient gene silencing
Lv, Y., Peng, R., Zhou, Y., Zhang, X., & Tan, W. (2015) · Chemical Communications · doi:10.1039/c5cc06937h · Cited by 27 · see citing works
Yu, H., Angelova, A., Angelov, B., Dyett, B., Matthews, L., Zhang, Y., Mohamad, M. E., Cai, X., Valimehr, S., Drummond, C. J., et al. (2023) · Angewandte Chemie · doi:10.1002/ange.202304977 · Cited by 26 · see citing works
Lipidoid Tail Structure Strongly Influences siRNA Delivery Activity
Knapp, C. M., Guo, P., & Whitehead, K. A. (2016) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-016-0436-9 · Cited by 26 · see citing works
Goldman, R., Murthy, N. T. V., Trent, N., Balakrishnan, A., Chivukula, S. V., Danz, H., Tibbitts, T. J., Dias, A., Vargas, J., Cooper, D. L., et al. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122243 · Cited by 26 · see citing works
Deng, Z. J., Morton, S. W., Bonner, D. K., Gu, L., Ow, H., & Hammond, P. T. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.02.013 · Cited by 25 · see citing works
Rapid access to phospholipid analogs using thiol-yne chemistry
Zhou, C. Y., Wu, H., & Devaraj, N. K. (2015) · Chemical Science · doi:10.1039/c5sc00653h · Cited by 24 · see citing works
Hausig, F., Sobotta, F. H., Richter, F., Harz, D. O., Traeger, A., & Brendel, J. C. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c00829 · Cited by 24 · see citing works
Tai, L., Liu, C., Jiang, K., Chen, X., Wei, G., Lu, W., & Pan, W. (2017) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2017.04.011 · Cited by 24 · see citing works
Designing hyperbranched polymers for gene delivery
Mou, Q., Ma, Y., Jin, X., & Zhu, X. (2016) · Molecular Systems Design & Engineering · doi:10.1039/c5me00015g · Cited by 24 · see citing works
Tanaka, H., Sato, Y., Nakabayashi, T., Tanaka, A., Nishio, K., Matsumoto, C., Matsumaru, A., Yamakawa, T., Ishizaki, K., Ueda, K., et al. (2025) · Nano Letters · doi:10.1021/acs.nanolett.4c06643 · Cited by 23 · see citing works
Oliveira, C. L., Silveira, I., Veiga, F., & Ribeiro, A. J. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.945421 · Cited by 23 · see citing works
Biodegradable cationic nanogels with tunable size, swelling and pKa for drug delivery
Spencer, D. S., Shodeinde, A. B., Beckman, D. W., Luu, B. C., Hodges, H. R., & Peppas, N. A. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119691 · Cited by 23 · see citing works
The development of tertiary amine cationic lipids for safe and efficient siRNA delivery
Lin, Z., Bao, M., Yu, Z., Xue, L., Ju, C., & Zhang, C. (2019) · Biomaterials Science · doi:10.1039/c9bm00494g · Cited by 23 · see citing works
Recent Advances in Lipid Nanoparticles: Nucleic Acid Therapeutics and Targeting Strategies
Sarmah, S., Baidya, S., & De, M. (2025) · Small · doi:10.1002/smll.202506812 · Cited by 25 · see citing works
mRNA vaccines: immunogenicity and quality characteristics
Quan, Y., Yang, H., Li, W., & Li, L. X. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03800-5 · Cited by 26 · see citing works
Lipid‐based nucleic acid therapeutics with in vivo efficacy
Sufian, M. A., & Ilies, M. A. (2022) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1856 · Cited by 22 · see citing works
Metwally, A. A., Nayel, A. A., & Hathout, R. M. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1042720 · Cited by 22 · see citing works
- Authors
- Alabi, C. A., Love, K. T., Sahay, G., Yin, H., Luly, K. M., Langer, R., & Anderson, D. G.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- University of Rochester (US)
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
- Harvard–MIT Division of Health Sciences and Technology (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-07-23
- Volume
- 110
- Issue
- 32
- Pages
- 12881-12886
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3740846
- OpenAlex
- W2155534998
- Cited by
- 188
- References
- 39
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 26 · 2023: 9 · 2022: 13 · 2021: 18 · 2020: 11 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 17 · 2015: 16 · 2014: 15 · 2013: 3
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (4r37eb000244-34)
- National Cancer Institute (P30CA014051)
- National Institute of Biomedical Imaging and Bioengineering (R37-EB000244)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- lipid nanoparticles, siRNA delivery, cellular uptake, in vitro to in vivo translation, nanocarrier design
- MeSH terms
- Animals, Factor VII, Flow Cytometry, HeLa Cells, Hemolysis, Humans, Lipids, Luciferases, Mice, Inbred C57BL, Reproducibility of Results, Gene Transfer Techniques, Microscopy, Confocal, Fluorescence Resonance Energy Transfer, RNA Interference, RNA, Small Interfering, Mice, Nanoparticles
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